Palladium-catalyzed arylation of enynes and electron-deficient alkynes using diaryliodonium salts

Article abstract of DOI:10.1021/ol015555t

matrix presentedA new single-pot procedure for the synthesis of aryl alkynes is described. Palladium catalyzes the coupling reaction of diaryliodonium compounds with enynes and electron-deficient alkynes to give aryl alkynes in good yields.

Full text of DOI:10.1021/ol015555t

ORGANIC
LETTERS
2001
Vol. 3, No. 6
859-860
Palladium-Catalyzed Arylation of Enynes
and Electron-Deficient Alkynes Using
Diaryliodonium Salts
Ukkiramapandian Radhakrishnan and Peter J. Stang*
Department of Chemistry, UniVersity of Utah, 315 South 1400 East,
Salt Lake City, Utah 84112
stang@chemistry.utah.edu
Received January 15, 2001
ABSTRACT
A new single-pot procedure for the synthesis of aryl alkynes is described. Palladium catalyzes the coupling reaction of diaryliodonium compounds
with enynes and electron-deficient alkynes to give aryl alkynes in good yields.
The palladium-catalyzed coupling of terminal alkynes with
aryl iodides to give arylalkynes is an important reaction in
organic chemistry (Sonogashira coupling).1,2 Alkynes ob-
tained in these reactions are useful building blocks in organic
and materials chemistry.3 However, this reaction has limita-
tions. Alkynes containing an electron-withdrawing group
(directly attached to the ethynyl carbon) do not react
significantly with aryl iodides;4 therefore, not many reports
appear in the literature.5 Also, palladium-catalyzed arylation
of enynes occurs only in moderate yields.6 Herein, we report
a new, efficient, and mild palladium-catalyzed method for
the arylation of enynes and electron-deficient alkynes using
diaryliodonium salts.
Iodonium compounds are widely available and generally
prepared under mild conditions.7 Aryliodonium salts show
superior reactivity compared to aryl halides. The highly
electron withdrawing nature of the PhI+ moiety in iodonium
compounds activates the carbon-iodine bond toward various
reactions.7 Diaryliodonium salts 1a and 1b were prepared
by a literature procedure.8
First, we investigated the coupling of a diaryliodonium
compound (1a) with a methyl enyne (2a) in the presence of
palladium as a catalyst and copper as a cocatalyst. Different
palladium sources and solvents were examined for this
coupling reaction; the PdCl2(PPh3)2/CuI/K2CO3 system was
found to be superior to other combinations. With this catalytic
system, reaction occurred at rt to give essentially a quantita-
tive yield of the aryl-substituted enyne 3a using either triflate
or tosylate as the counterion (Table 1, entries 1 and 2).
(1) Metal-Catalyzed Cross Coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: London, 1998.
Terminal alkynes containing an electron-withdrawing
group directly attached to the ethynyl carbon atom do not
react significantly with aryl halides. Therefore, generally an
alternative methodology is used to prepare aryl propiolic
(2) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975,
4467-4470. (b) Nakamura, K.; Okubo, H.; Yamaguchi, M. Synlett 1999,
549-550.
(3) (a) Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.;
VCH: Weinheim, 1995. (b) Brandsma, L.; Vasilevsky, S. F.; Verkruijsse,
H. D. Application of Transition Metal Catalysts in Organic Synthesis;
Springer: Berlin, 1998; p 198.
(4) (a) Yoneda, N.; Matsuoka, S.; Miyaura, N.; Fukuhara, T.; Suzuki,
A. Bull. Chem. Soc. Jpn. 1990, 63, 2124-2126. (b) Sakamoto, T.; Shiga,
F.; Yasuhara, A.; Uchiyama, D.; Kondo, Y.; Yamanaka, H. Synthesis 1992,
746-748. (c) Kundu, N. G.; Dasgupta, S. K. J. Chem. Soc., Perkin Trans.
1 1993, 2657-2663.
(5) Eckert, T.; Ipaktschi, J. Synth. Commun. 1998, 28, 327-335.
(6) Iwasawa, N.; Satoh, H. J. Am. Chem. Soc. 1999, 121, 7951-7952.
(7) (a) Stang, P. J.; Zhdankin, V. V. Chem. ReV. 1996, 96, 1123-1178.
(b) Varvoglis, A. HyperValent Iodine in Organic Synthesis; Academic
Press: London, 1997. (c) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271-
1287.
(8) (a) Koser, G. F.; Wettach, R. H.; Smith, C. S. J. Org. Chem. 1980,
45, 1543-1544. (b) Stang, P. J.; Zhdankin, V. V.; Tykwinski, R.; Zefirov,
N. S. Tetrahedron Lett. 1991, 32, 7497-7498.
10.1021/ol015555t CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/01/2001

Coupling of iodonium salt 1c and methyl enyne 2a proceeded
smoothly to give product 3f (70%) (Scheme 1). The phenyl
Table 1. Palladium-Catalyzed Arylation of Alkynes9
Scheme 1. Unsymmetrical Iodonium-Enyne Coupling
ring with the electron-donating group (TMS) underwent
coupling to give the corresponding arylated product.
A plausible mechanism for this coupling reaction is
depicted in Scheme 2. The reaction most likely begins with
Scheme 2. Proposed Mechanism of Coupling Reactions
the oxidative addition of Pd0 to the iodonium compound to
give arylpalladium species 4 which on reaction with copper
acetylide leads to the aryl(alkynyl)palladium species 5 that
on extrusion of Pd0 leads to the formation of aryl alkyne 3.
Both the palladium and copper(I) iodide were essential
catalysts for this reaction. The aryl iodides obtained as
byproduct lends support to our mechanism.
In summary, we have developed a new, superior, and mild
protocol for the arylation of enynes and electron-deficient
alkynes using aryliodonium salts as the electrophilic coupling
partners, where aryl iodides either do not work or give only
low yields of products.
a Isolated yields: cyhex, cyclohexane, Ad, adamantane.
esters4b and acetylenic ketones.4c,10 In contrast, the aryliodo-
nium salts underwent coupling with alkynes containing
electron-withdrawing groups such as ester 2b and ketones
2c,11 2d, and 2e to give arylated products in good yield (Table
1, entries 3-6).
It was also of interest to study this reaction using
unsymmetrically substituted iodonium salts. Aryliodonium
1c was obtained using a modified literature procedure.12
Acknowledgment. We thank the NIH (GM-57052) for
financial support.
(9) Typical procedure: To a mixture of PdCl2(PPh3)2 (0.021 g, 0.03
mmol), 1a (0.643 g, 1.5 mmol), CuI (0.04 mmol), and K2CO3 (0.276 g, 2
mmol) in DMF/H2O (6:1) (14 mL) was added enyne 2a (0.099 g, 1.5 mmol)
at rt under an N2 atmosphere, and the solution was stirred at rt for 2-3 h.
The reaction was quenched by an aqueous NH4Cl solution; workup and
column chromatography (silica gel, hexane) gave 3a (0.21 g, 99%).
(10) Tohda, Y.; Sonagashira, K.; Hagihara, N. Synthesis 1977, 777-
778.
Supporting Information Available: A description of
experimental details and 1H NMR spectra of the compounds
3d, 3e, and 3f. This material is available free of charge via
the Internet at http://pubs.acs.org.
(11) Muzart, J.; Ajjou, A. N. A. Synthesis 1993, 785-787.
(12) Kuehl, C. J.; Bolz, J. T.; Zhdankin, V. V. Synthesis 1995, 312-
316.
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